MEDI5395 Advanced Solid Tumors

Overview

About this study

The purpose for this study is to find out if MEDI5395 and durvalumab will work and be safe for the treatment of solid tumors.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria: 

  • At least 18 years old at screening
  • 2 Body weight > 35 kg at screening
  • Written informed consent and any locally required authorization (e.g., data privacy) obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations 4 The subject must consent to take precautionary measures to prevent NDV transmission to humans and birds, from the day of the first dose of MEDI5395 through 4 weeks after the last dose of MEDI5395, including:
    • Avoid all contact with birds, including pets and farm animals;
    • Avoid close contact with individuals who have regular contact with birds (e.g., bird keepers or poultry workers);
    • Avoid close contact with individuals with weakened immune systems, including those with AIDS; cancer and transplant patients who are taking certain immunosuppressive drugs; and those with inherited diseases that affect the immune system.
  • Histologic documentation (unless noted below) of one of the advanced solid tumors. Received and have progressed, are refractory, or are intolerant to standard therapy for the specific tumor type. All subjects are required to have had at least one prior line of treatment in the recurrent or metastatic (R/M) setting
  • Subjects must have at least 1 lesion that is measurable by RECIST v1.1 (Eisenhauer et al, 2009) and an additional non-lymph node non-target lesion that can be biopsied at acceptable risk as judged by the investigator.
    • Note: if a non-target lesion is not available or cannot be biopsied, a RECIST target, non-lymph node lesion, lesion ≥ 2 cm in longest diameter may be used for non-excisional biopsy. A previously irradiated lesion can be considered a target lesion if the lesion is well-defined and has clearly progressed during or after the most recent therapy.
  • ECOG performance status of 0 to 1 9 Must have a life expectancy of at least 12 weeks, as estimated through the Gustave Roussy Immune Score (GRIm-Score) (Bigot et al, 2017); i.e., must meet no more than 1 of the following criteria (on at least one set of screening laboratory measures drawn on same day):
    • Albumin < 3.5 g/dL;
    • Lactate dehydrogenase (LDH) > ULN;
    • Neutrophils-to-lymphocyte ratio (NLR) > 6;
  • Adequate organ function within 14 days of first dose of MEDI5395 as defined in: 
    • Absolute neutrophil count > 1500 cells/μL;
    • White blood cells ≥ 3000 cells/μL;
    • Hemoglobin ≥ 9 g/dL;
    • Platelets ≥ 100,000/μL;
    • Hepatic ALT ≤ 2.5 × ULN;
    • AST ≤ 2.5 × ULN;
    • TBL ≤ 1.5 × ULN [≤ 3 × ULN if the subject has documented Gilbert’s syndrome];
    • Albumin ≥ 3 g/dL;
    • Renal Creatinine clearance ≥ 40 mL/min calculated by Cockcroft-Gault (using actual body weight) or by measured 24-hour urine collection.
    • ALT = alanine aminotransferase;
    • AST = aspartate aminotransferase;
    • TBL = total bilirubin;
    • ULN = upper limit of normal.
  • Females of childbearing potential who are not abstinent and intend to be sexually active with a nonsterilized male partner must have used at least one highly effective method of contraception from the time of screening throughout the total duration of the drug treatment and the drug washout period (6 months after the last dose of durvalumab). Non-sterilized male partners of a female subject of childbearing potential must use a male condom plus spermicide throughout this period. Cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Female subjects should refrain from breastfeeding or egg donation throughout this period.
  • Nonsterilized male subjects who are not abstinent and intend to be sexually active with a female partner of childbearing potential must use a male condom with spermicide from the time of screening throughout the total duration of the drug treatment and the drug washout period (6 months after the last dose of durvalumab). Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Male subjects should refrain from sperm donation throughout this period.
  • Female partners (of childbearing potential) of male subjects must also use a highly effective method of contraception throughout this period
  • Women of childbearing potential are defined as those who are not surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as amenorrhea for 12 months without an alternative medical cause). The following age-specific requirements apply to the definition of postmenopausal status:
    • Women < 50 years of age would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle stimulating hormone levels in the post-menopausal range for the institution;
    • Women ≥ 50 years of age would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced oophorectomy with last menses > 1 year ago, had chemotherapy-induced menopause with > 1-year interval since last menses, or underwent surgical sterilization (bilateral oophorectomy or hysterectomy);
    • Women who are surgically sterile (i.e., bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy) are eligible.

Exclusion Criteria:

  • Rapidly progressing disease defined as a subject that cannot tolerate a break of at least 8 weeks from systemic anticancer therapy.
  • Primary central nervous system (CNS) disease is excluded, as well as untreated or uncontrolled metastatic CNS involvement, leptomeningeal disease, or cord compression. NOTE: CNS disease that has been treated and stable/controlled for at least 3 months is permitted. Subjects with CNS disease controlled via systemic steroids are not permitted.
  • Prior to the first dose of MEDI5395:
    • At least 28 days must have elapsed since prior anti-PD-1, anti-PD-L1, anti-CTLA-4 or other check point inhibitor immunotherapy;
    • At least 90 days must have elapsed since oncolytic virus therapy;
    • At least 28 days must have elapsed since non-immunotherapy monoclonal antibody treatment (for example trastuzumab, cetuximab, bevacizumab, or panitumumab);
    • At least 90 days must have elapsed since prior anthracycline treatment and total cumulative dose must not exceed 450 mg/m^2 for doxorubicin or 900 mg/m^2 for epirubicin.
  • History of severe allergic reactions to any of the study drug components.
  • Pregnant, intending to become pregnant, or breastfeeding.
  • Infectious disease exclusions:
    • Receipt of live, attenuated vaccine within 28 days prior to the first dose of MEDI5395;
    • Note: Subjects, if enrolled, should not receive live vaccine during the study and for 60 days after the last dose of MEDI5395 or 30 days after the last dose of durvalumab, whichever is longer.
    • Active bacterial, fungal, or viral infections (including cold, SARS-CoV-2, or influenza). All prior infections must have resolved following optimal therapy and subject must be off all systemic anti-infective agents for a week prior to first dose of MEDI5395 (with the exception of acyclovir, entecavir, lamivudine, tenofovir, and valacyclovir);
    • History of tuberculosis;
  • Positive viral disease test results during screening, including
    • Positive human immunodeficiency virus (HIV) antibody;
    • Positive hepatitis A immunoglobulin M;
    • Positive hepatitis B surface antigen or positive hepatitis B core antibody, with the exception of subjects who are receiving entecavir, lamivudine, or tenofovir (either prophylactically or for management) and have undetectable hepatitis B virus load by quantitative PCR;
    • with evidence of fully recovered past infection who developed immunity (anti-HBs positive; anti-HBc positive; HBsAg negative, undetectable Hepatitis B viral load);
    • Positive hepatitis C virus (HCV) antibody, unless hepatitis C RNA is undetectable by quantitative PCR on 2 occasions at least 4 weeks apart;
    • Positive SARS-CoV-2 diagnostic test at screening 9 Any conditions requiring use of any systemic immunosuppressant including systemic corticosteroids, methotrexate, azathioprine, tumor necrosis factor (TNF) inhibitor, and/or interleukin 6 (IL-6) blockers.
  • Any active autoimmune disease or chronic inflammatory condition, with the following exceptions:
    • Vitiligo or alopecia;
    • Hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement;
    • Any chronic skin condition that does not require systemic therapy;
    • Celiac disease that is controlled by diet alone;
    • Diverticulosis.
  • Active acquired immune-deficiency states including but not limited to myelodysplastic disorders, marrow failures, HIV infection, history of organ allograft, or recent (within 6 months) pregnancy.
  • History of primary immunodeficiency.
  • Subjects with a history of bleeding disorders or thromboembolic events within 3 months prior to enrollment.
  • Subjects who have worked in the poultry industry within the last 3 months or who are regularly exposed to poultry or birds 15 Current active hepatitis or biliary disease (except for Gilbert’s syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment); this includes subjects with liver tumors that, based on size, location, and/or lack of prior stent placement, are at risk of causing biliary tract obstruction or hepatic failure in the event of tumor inflammation during treatment.
  • Clinically significant pulmonary disease exclusions:
    • Clinically significant pleural effusion causing symptoms or needing intervention;
    • Oxygen saturation less than 90% on room air;
    • Lung tumors that, in the judgement of the investigator, based on size and/or location are encasing or in close proximity to crucial structures (e.g., carotid artery, jugular vein, trachea, etc.) and deemed at risk of causing significant impairment in the event of tumor inflammation during treatment.
  • Cardiac disease exclusions:
    • New York Heart Association Class 3 or 4 heart failure;
    • Uncontrolled hypertension, unstable angina pectoris;
    • Clinically important cardiac arrhythmia (e.g., requiring anti-arrhythmic drugs);
    • Mean QT interval corrected for heart rate (QTc) ≥ 480 ms calculated from the triplicate ECGs using Fredericia's correction (QTcF);
    • Myocardial infarction within 6 months prior to enrollment;
    • Left ventricular ejection fraction (LVEF) < 40% by echocardiogram (ECHO) performed at screening;
    • History of myocarditis from any cause.
    • Diagnosis of a second malignancy within the last 2 years prior to the first dose of MEDI5395 except for those with a negligible risk of metastasis or death, treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent).
    • Major surgery (as defined by the investigator) within 4 weeks prior to first dose of MEDI5395 or still recovering from prior surgery. Local surgical removal of isolated lesions for palliative intent is acceptable.
    • Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring AEs from MEDI5395, or compromise the ability of the subject to give written informed consent.
    • Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results.

Eligibility last updated 8/26/21. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Mitesh Borad, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Evanthia Galanis, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Study Results Summary

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Supplemental Study Information

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Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

International patient clinical studies questions